目的 探究人参皂苷Rg₁对APP/PS1双转基因模型小鼠认知障碍、氧化应激损伤、炎症反应、Aβ堆积和神经细胞凋亡的改善作用。方法 采用Morris水迷宫实验，对APP/PS1模型小鼠的认知功能进行评价；采用试剂盒和ELISA法对各组小鼠氧化损伤和炎症相关指标进行测定；采用HE染色和Western blotting法对各组小鼠海马组织神经元凋亡及凋亡相关蛋白进行定量分析。结果 人参皂苷Rg₁能够显著改善APP/PS1双转基因模型小鼠的认知功能，降低Aβ堆积及丙二醛（MDA）水平，提高超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-P_X）、过氧化氢酶（CAT）活性。此外，人参皂苷Rg₁还可通过显著性降低APP/PS1小鼠血清肿瘤坏死因子-α（TNF-α）、γ干扰素（IFN-γ）、白细胞介素-1β（IL-1β）和IL-6水平，增加IL-2水平，从而抑制神经炎症反应。HE染色显示人参皂苷Rg₁能降低海马细胞的凋亡状态。人参皂苷Rg₁还可以显著升高海马中Bcl-2/Bax的值，并显著降低Caspase-3、Caspase-9和Cyt-c蛋白的表达水平。结论 人参皂苷Rg₁能够显著改善APP/PS1模型小鼠的氧化应激状态，减轻炎症反应，抑制神经元凋亡和改善认知功能。

Objective To investigate the effects of ginsenoside Rg₁ on cognitive impairment, oxidative stress injury, inflammation, accumulation of A beta and neuronal apoptosis in APP/PS1 mice. Methods Morris water maze test was used to evaluate the cognitive function of APP/PS1 mice. The oxidative damage and inflammation related indexes of APP/PS1 mice in each group were measured by kit and Elisa. The apoptotic and apoptotic proteins of hippocampal neurons in each group were quantified by HE staining and Western blot. Results The results showed that Rg₁ could significantly improve the cognitive function of mice, reduce the accumulation of Aβ and the content of malondialdehyde (MDA), and increase the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT). In addition, Rg₁ could significantly reduce the serum levels of TNF-α, INF-γ, IL-1β and IL-6 in APP/PS1 mice, and increase the level of IL-2, thereby inhibiting the neuroinflammatory response. HE staining showed that Rg₁ could reduce the apoptotic state of hippocampal cells. Rg₁ also significantly increased the expression of Bcl-2/Bax protein ratio, and reduced the expression of Caspase-3, Caspase-9 and Cyt-c protein in hippocampus. Conclusion Rg₁ can significantly improve oxidative stress, reduce inflammatory response, inhibit neuronal apoptosis and improve cognitive function in APP/PS1 mice.

R285.5

河南省重点科技攻关项目（092102310028）